Variants of the α6β1Laminin Receptor in Early Murine Development: Distribution, Molecular Cloning and Chromosomal Localization of the Mouse Integrin α6Subunit

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Abstract
Laminin (A:B1:B2) is a major component of the first basement membrane to appear in the developing mouse embryo. Its effects on morphogenesis and differentiation are mediated by interaction with cell surface receptors that are members of the integrin family. We have studied the expression of the α6 subunit of murine α6β1 and its ligand, laminin, in preimplantation mouse embryos, embryo outgrowths and in embryonic stem (ES) cells and embryonal carcinoma (EC) cells. The α6 subunit is present in the oocyte and throughout preimplantation development. Laminin A chain appears later than α6 and has a more restricted distribution until the late blastocyst stage. α6β1 is strongly expressed in ES and EC cells; the levels of mRNA expression are not altered by differentiation. Molecular cloning of cDNA for the murine integrin α6 subunit from a mammary gland γt11 library showed, as in man, an open reading frame encoding two variants of α6, α6 and α6B. The identity of the α6 amino acid sequence to that in man and chicken is 93% and 73%, respectively. The gene for murine α6 was mapped to chromosome 2. While undifferentiated ES and EC cells express only α6B, α6A is co-expressed in ES cells after differentiation is induced by retinoic acid. α6B is also the only variant expressed in blastocyst stage embryos, but when blastocysts have grown out in culture both α6A and α6B are expressed reflecting the results in the cell lines. We suggest that the deposition of laminin in the embryo is a receptor-mediated process and that the shift in the expression of the variants, as the inner cell mass forms its first differentiated progeny, reflects a change in functional properties.